The overarching hypothesis of this proposal is that rapid closure of mucosal wounds originates with intrinsic cellular characteristics of oral keratinocytes that differ from those of the skin. The current goal of this research is to compare oral mucosa and skin would healing in order to determine the characteristics of oral mucosa that lead to rapid and minimal scar repair. The long-term goal of this research is to determine molecular mechanisms that lead to swift oral mucosal healing and not in skin. The following specific aims were developed to elucidate the mechanisms by which oral keratinocytes mediate the swift re- epithelialization of oral wounds: I. Identify factors that allow swift re-epithelialization of oral mucosa wounds in comparison to skin wounds. A. Assess proliferation in oral and skin keratinocytes in in vivo wound models. B. Compare growth factor expression in excisional mouse wounds at both oral mucosal and cutaneious sites. II. Identify intrinsic differences between human oral and skin keratinocytes important for wound closure, and assess the contribution of proliferation and migration to this process. A. Compare the proliferative capacity of oral versus skin kerotinocytes using an in vivo wound model. B. Determine if critical oral mucosal growth factors can transform the phenotype of skin keratinocytes to that of rapidly healing oral mucosal keratinocytes in vitro. A critical void in our understanding of the differences between cutaneous and oral repair currently exists. The completion of theproposed aims will provide novel mechanistic information about the divergent patterns of oral and skin wound healing. Ultimately, such knowledge may assist in the design of therapeutic strategies to enhance tissure repair. Relevance: While most persons exhibit adequate and appropriate wound healing, an estimated one millions persons in the U.S. suffer from wound healing problems each year. The medical benefits from improved healing may include shorter hospitalization time, reduced requirements for split-thickness autographs, and reduced long-term morbidity after recovery.